Coronary artery disease produces regional perfusion deficits which lead to arrhythmias and make it difficult to predict drug concentrations in ischemic myocardium from blood levels of drugs. Lidocaine and propranolol exert greater electron physiologic effects in ischemic than in normal zones of the dog heart. We propose studies in dogs with coronary occlusions which combine several experimental approaches: recording local electrograms, hemodynamics regional myocardial blood flow (MBF) and the distribution of 14C-lidocaine or 14C-propranolol. We are developing techniques to count 14C-drugs in the same samples as gamma-emitting microspheres. Our objectives are to determine (1) the relative quantities of the 14C-drug in the normal and ischemic zones, (2) whether drugs localize in a particular transmural or border region, or in Purkinje fibers, (3) the relation between drug distribution and each of the following: MBF, electrophysiologic effects, duration of ischemia/infarction, and time after 14C-drug bolus injection. (4) Finally, we plan to determine whether antiarrhythmic drugs or nitroglycerin can redistribute MBF and 14C-drug toward ischemic zones. We will evaluate whether the combination of nitroglycerin and 14C-antiarrhythmic drugs will enhance electrophysiologic effects of antiarrhythmic drugs. Our intergrated approach to investigating antiarrhythmic drugs should provide a broader perspective on the mechanisms involved. Also, since one cannot predict whether a 14C-drug will have a lower or higher concentration relative to blood flow in ischemic myocardium, our studies may indicate a drug which would be useful as a diagnostic agent for radioisotopic imaging in patients, using a different isotopic label.